Schmidt, P. J., Nieman, L. K., Danaceau, M. A., Adams, L. F., & Rubinow, D. R. (1998). Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. The New England Journal of Medicine, 338(4), 209-216. https://doi.org/10.1056/NEJM199801223380401
Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med. 1998;338(4):209-216. doi:10.1056/NEJM199801223380401
Schmidt, Peter J., et al. "Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome." The New England Journal of Medicine, vol. 338, no. 4, 1998, pp. 209-216.
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Estradiol or progesterone brought PMS symptoms back in 10 women
In a small NIH trial, estradiol or progesterone brought symptoms back in the 10 women with premenstrual syndrome whose symptoms eased on leuprolide. The 15 women without it had no mood changes on the same hormones. Researchers randomized 20 women with the syndrome to leuprolide or placebo. The hormone phase followed in 10 of the 18 who received leuprolide.
Key Findings
Ten women with premenstrual syndrome received leuprolide and 10 received placebo. Almost all week 4 symptom scores were significantly lower on leuprolide than at baseline and than on placebo.
No woman responded to placebo. Eight of 18 women given leuprolide had no response: 4 of 10 double-blind and 4 of 8 open-label. The other 10 entered the hormone phase.
Adding estradiol or progesterone during continued leuprolide brought back sadness, anxiety, bloating, impaired function and irritability in the 10 women with the syndrome. The 15 women without it stayed asymptomatic.
In the women with the syndrome, symptoms peaked one or two weeks after estradiol or progesterone began. Symptoms were milder during the last week of replacement.
Five women with the syndrome who received placebo hormone had no changes in mood.
Interpretation
The leuprolide comparison was randomized and double-blind, though blinding could not be kept for women on placebo beyond two months. The hormone phase was a double-blind crossover in only 10 women with the syndrome. Only women whose symptoms eased on leuprolide entered it, so the results describe responders. The women without the syndrome averaged 30 years old and the women with it averaged 37. The authors suggest that normal hormone levels can trigger a mood decline in susceptible women. They cannot predict whether long-term or low-dose replacement would keep causing symptoms.
RRM Context
Leuprolide suppresses the ovaries and eased symptoms in 10 of 18 women. The authors suggest that susceptible women respond abnormally to normal hormone levels. Restorative reproductive medicine treats a cycle-linked symptom as a question of cause. Cycle-charting-informed care uses daily records like the ones these researchers collected for three months.
Our editorial summary of this paper, not the article's abstract.
Abstract
Background
The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome.
Methods
We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales.
Results
The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration.
Conclusions
In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.
